Phospholipase C beta 4 and protein kinase C alpha and/or protein kinase C beta I are involved in the induction of long term depression in cerebellar Purkinje cells

Activation of the type-1 metabotropic glutamate receptor (mG1uR1) signaling pathway in the cerebellum involves activation of phospholipase C (PLC) and protein kinase C (PKC) for the induction of cerebellar long term depressio n (LTD). The PLC and PKC isoforms that are involved in LTD remain unclear, however. One previous study found no change in LTD in PKC gamma -deficient mice, thus, in the present study, we examined cerebellar LTD in PLC beta4-d eficient mice. Immunohistochemical and Western blot analyses of cerebellum from wild-type mice revealed that PLC beta1 was expressed weakly and unifor mly, PLC beta2 was not detected, PLC beta3 was expressed predominantly in c audal cerebellum (lobes 7-10), and PLC beta4 was expressed uniformly throug hout. In PLC beta4-deficient mice, expression of total PLC beta, the mGluR1 -mediated Ca2+ response, and LTD induction were greatly reduced in rostral cerebellum (lobes 1-6). Furthermore, we used immunohistochemistry to locali ze PKC alpha, -betaI, -beta II, and -gamma in mouse cerebellar Purkinje cel ls during LTD induction. Both PKC alpha and PKC betaI were found to be tran slocated to the plasmamembrane under these conditions. Taken together, thes e results suggest that mG1uR1-mediated activation of PLC beta4 in rostral c erebellar Purkinje cells induced LTD via PKC alpha and/or PKC betaI.